‘Landmark’ study provides an unprecedented glimpse of the mysterious phase of the human embryo

An unprecedented glimpse of the human embryo at an early stage of development has provided critical clues as to how undifferentiated cells become the specialized ones we are made of, researchers reported Wednesday.

When an embryo begins to form, it is composed of stem cells with the potential to become any part of the body, from brain tissue to bone tissue.

Human stem cells begin to take on these specific roles during a process called gastrulation that occurs in the third week after fertilization.

Until now, that process has mostly been a black box, inaccessible for direct viewing.

Ethical rules mean that laboratory-grown stem cells can only be grown artificially for two weeks. It is also impossible to observe gastrulation during pregnancy.

The new results, published in Nature, provide direct data on how the transformation of stem cells takes place.

Experts not involved in the study hailed it as a “landmark” and a “Rosetta Stone” for future research in developmental biology.

Until now, scientists have relied on samples from mice and non-human primates to better understand gastrulation, but the degree of similarity with the process in humans was always in doubt.

The data presented on Wednesday provide a basis for measuring how useful experiments on other mammals have been and will be in the future.

No neurons

Human cells contain all of a person’s genetic material, but gastrulation marks the initial stage when certain genes are turned on.

It is the first step in determining whether a cell becomes part of our blood, for example, or a brain cell.

“You have a kind of explosion of cell diversity,” study author Shankar Srinivas of Oxford University told reporters at an online press conference, describing the process as “beautiful.”

The cells that make up an embryo begin to accumulate in specific regions at this stage.

Srinivas’ team dissected the sample of a donated human embryo and then used a process called single-cell RNA sequencing to determine which genes were active in each of the more than 1,000 individual cells.

The resulting map shows which cells had been activated to take on specific roles and where they were located in the week-old embryo.

By matching the results with observations of museum embryos, the researchers found more similarities than differences.

“A mouse is actually a very good model of a human,” Srinivas said.

However, there were important differences, such as the presence of proto-blood cells in humans much earlier than in mice.

And scientists also noted an important absence: While museum embryos at this stage would have begun to develop a nervous system, no such material was present in the human sample.

This finding could help raise the 14-day limit for culturing embryos for examination, which was set to completely exclude examination of an embryo with even the onset of a nervous system.

Rare sample

Both scientists involved in the study and external observers noted the unusual rarity of the sample, which was taken from the Human Developmental Biology Resource in the UK.

“Most people would not even know they were pregnant in the 16 days after conception,” Srinivas said, “but this person did, got the notice and generously gave the test.”

Srinivas said before that his laboratory spent five years on a waiting list – and that a change in the rules for how terminated embryos are collected will probably mean a much longer waiting time in the future.

His team performed genomic tests and physical examinations to determine that the sample was a good representation of normal human development.

But they also said that it would be ideal to have more such samples to compare and that a change in the rules may be necessary to allow that to happen.

“It’s a landmark paper that many will base their future findings on,” said geneticist Darren Griffin of the University of Kent.

Stem cell biologist Harry Leitch of Imperial College London called it “an invaluable resource” that will “facilitate further progress in stem cell biology and regenerative medicine”.

© Agence France-Presse


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